Volume 180 - Issue 8
Parallel infusion of hydrocortisone ± chlorpheniramine bolus injection to prevent acute adverse reactions to antivenom for snakebites
Author: Simon G A Brown
Med J Aust 2004; 180 (8): 428-429. || doi: 10.5694/j.1326-5377.2004.tb06003.x
Published online: 19 April 2004
Published online: 19 April 2004
Simon G A Brown
Emergency Physician, Fremantle Hospital & Health Service, and Clinical Senior Lecturer in Emergency Medicine, University of Western Australia, Department of Emergency Medicine, Fremantle Hospital, Alma Street, Fremantle, WA 6160. simon.brownAThealth.wa.gov.au
To the Editor: Gawarammana et al present an interesting study of premedication to prevent adverse reactions to snake antivenom,1 but I have concerns with the data presentation and analysis. The 95% confidence intervals presented in Box 3 of their article are impossibly narrow. For example, recalculation of the first cell (hypotension rate for treatment A) by the binomial method gives a 95% confidence interval of 12%–62%, not 30%–36% as presented. Also, my analysis of the aggregate endpoint differs. Using the Fisher exact test to compare reaction rates in the hydrocortisone + antihistamine group (11/21) with placebo (13/16), for the difference in proportions of 0.29 I obtain a 95% confidence interval of 2 0.04 to 0.58. This has a P value of 0.14 using a 2-tailed test, according to the program Analyse-it.2
This comes as no surprise given that steroids take hours to work, and that histamine is just one of many mediators released during anaphylaxis, rising early and only transiently during severe and protracted anaphylactic reactions.3 Although antihistamines reverse the effects of histamine infusions which mimic anaphylaxis, animal studies indicate that they are ineffective for treating anaphylaxis mediated by mast-cell degranulation.4,5
Human studies have shown that H1 blockade is useful in preventing mild reactions to immunotherapy that are confined to the skin, but do not appear to prevent severe reactions.6,7 One human study has compared H1 + H2 blockade with H1-only blockade for the management of mild allergic reactions, finding a small benefit of combined H1 + H2 blockade.8 However, a confounder was that adrenaline was administered more frequently in the combined H1 + H2 antihistamine treatment group. A study of reactions to immunotherapy has failed to show any benefit from H1 + H2 blockade.7
I suspect that, instead of proceeding to study combination prophylaxis with antihistamines, steroids and adrenaline, it might be better to examine the preparation for and management of allergic reactions to antivenom. Many doctors fear intravenous adrenaline infusions, but in our experience this approach to managing anaphylaxis is safe, well tolerated and immediately effective, without the unpredictable, unpleasant, and (in the setting of venom-induced coagulopathy) potentially dangerous side effects sometimes seen with intramuscular, subcutaneous and intravenous bolus injections.9 Perhaps it is time for a trial of premedication with subcutaneous adrenaline versus an “as required” approach using a carefully titrated intravenous infusion.
References
- Gawarammana IB, Kularatne SAM, Dissanayake WP, et al. Parallel infusion of hydrocortisone ± chlorpheniramine bolus injection to prevent acute adverse reactions to antivenom for snakebites. Med J Aust 2003; 180: 20-23.<eMJA full text>
- Analyse-it for Microsoft Excel [computer program]. Version 1.61. Leeds, UK: Analyse-it Software Ltd, 2001. CHDEADHH
- Smith PL, Kagey-Sobotka A, Bleecker ER, et al. Physiologic manifestations of human anaphylaxis. J Clin Invest 1980; 66: 1072-1080. i1083068
- Silverman HJ, Taylor WR, Smith PL, et al. Effects of antihistamines on the cardiopulmonary changes due to canine anaphylaxis. J Appl Physiol 1988; 64: 210-217. CHDIFDIH
- Felix SB, Baumann G, Hashemi T, et al. Characterization of cardiovascular events mediated by platelet activating factor during systemic anaphylaxis. J Cardiovasc Pharmacol 1990; 15: 987-997. CHDJCBFF
- Berchtold E, Maibach R, Muller U. Reduction of side effects from rush-immunotherapy with honey bee venom by pretreatment with terfenadine. Clin Exp Allergy 1992; 22: 59-65. CHDJEBJJ
- Brockow K, Kiehn M, Riethmuller C, et al. Efficacy of antihistamine pretreatment in the prevention of adverse reactions to Hymenoptera immunotherapy: a prospective, randomized, placebo-controlled trial. J Allergy Clin Immunol 1997; 100: 458-463. CHDEGJCB
- Lin RY, Curry A, Pesola GR, et al. Improved outcomes in patients with acute allergic syndromes who are treated with combined H1 and H2 antagonists. Ann Emerg Med 2000; 36: 462-468. CHDDFJFF
- Brown SGA, Blackman KE, Stenlake V, Heddle RJ. Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation. Emerg Med J 2004; 21: 149-154. i1083080